NCT03247088

Sorafenib, Busulfan and Fludarabine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia Undergoing Donor Stem Cell Transplant

Phase I/II Study of Sorafenib Added to Busulfan and Fludarabine Conditioning Regimen in Patients With Relapsed/Refractory AML Undergoing Stem Cell Transplantation

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 74 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the best dose of sorafenib when given together with busulfan and fludarabine in treating patients with acute myeloid leukemia that has come back or does not respond to treatment and who are undergoing donor stem cell transplant. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as busulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving sorafenib with busulfan and fludarabine may work better in treating patients with recurrent or refractory acute myeloid leukemia.

Detailed description

PRIMARY OBJECTIVES: I. To identify the maximum tolerated dose (MTD) of sorafenib when combined with busulfan and fludarabine conditioning regimen. II. To obtain preliminary evidence of efficacy. SECONDARY OBJECTIVES: I. To determine safety of this regimen as per National Cancer Institute (NCI) toxicity criteria. II. To determine time to neutrophil and platelet engraftment. III. To determine incidence of acute and chronic graft versus host disease (GVHD). IV. To determine relapse incidence. V. To determine non relapse mortality. VI. To determine overall survival. TERTIARY OBJECTIVES: I. To study chemotherapy resistance. II. To study deoxyribonucleic acid (DNA) damage. III. To study immune recovery and cytokines (both in plasma and cells). OUTLINE: This is a phase I, dose escalation study of sorafenib, followed by a phase II study. PRE-STEM CELL INFUSION: Patients receive sorafenib orally (PO) once daily (QD) or twice daily (BID) on days -24 to -5, busulfan intravenously (IV) over 3 hours on days -20 and -13 and -6 and -3, and fludarabine IV over 1 hour on days -6 to -3 in the absence of disease progression or unacceptable toxicity. STEM CELL INFUSION: Patients receive allogeneic hematopoietic stem cell transplant (HSCT) IV in the absence of disease progression or unacceptable toxicity. POST-STEM CELL INFUSION: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus PO BID beginning day 5 for about 50 days, filgrastim subcutaneously (SC) on day 7 and sorafenib PO BID beginning between days +30 and +120 for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with matched unrelated donor receive mycophenolate mofetil PO thrice daily (TID) or IV over 2 hours TID beginning on day 5 for up to 90 days for longer.

Conditions

• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
PROCEDURE	Allogeneic Hematopoietic Stem Cell Transplantation	Undergo allogeneic HSCT IV
DRUG	Busulfan	Given IV
DRUG	Cyclophosphamide	Given IV
BIOLOGICAL	Filgrastim	Given SC
DRUG	Fludarabine	Given IV
DRUG	Mycophenolate Mofetil	Given PO
DRUG	Sorafenib	Given PO
DRUG	Tacrolimus	Given PO

Timeline

• Start date: 2017-07-30
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2017-08-11
• Last updated: 2025-12-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study